Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

Despite its rarity, cutaneous melanoma (CM) represents the deadliest skin cancer with a high mortality rate, an incidence on rise, and limited therapeutic options at present. Melanin is polymeric pigment naturally produced within melanocytes CM cells that gained noteworthy attention due to pharmacological properties, potential for design of nanoplatforms biomedical applications. Up date, utilization melanin-like nanoparticles (MEL-NPs) in treatment has been well-documented, although their efficacy therapy remains scarcely investigated. The current study presents preclinical evaluation MEL-NPs as nanomedicine management. were through oxidative polymerization dopamine characterized via electron microscopy UV-VIS spectroscopy. antioxidant activity was determined by using DPPH method. cytotoxic, anti-migratory, anti-clonogenic, pro-oxidant pro-apoptotic properties investigated vitro applying MTT viability test, bright-field immunofluorescence microscopy, DCFDA/H2DCFDA scratch assay, colony formation RT-qPCR. irritant anti-angiogenic effects assessed ovo vascularized chorioallantoic membrane (CAM). as-made presented spherical morphology, average size 85.61 nm, broad absorption spectrum, strong activity. After 24 h treatment, exerted selective cytotoxicity SH-4 B164A5 compared HEMa, HaCaT, JB6 Cl 41-5a healthy cells, except concentration 100 µg/mL, which declined under 70%. Additionally, accumulated intracellular space forming perinuclear coating, inhibited motility clonogenic potential, increased stress, targeted epithelial-to-mesenchymal transition, induced apoptosis altering cell nuclear aspect, F-actin tubulin distribution, modulating expression pro- anti-apoptotic markers. In ovo, lacked vascular toxic effects, while exerting angio-suppressive demonstrated promising anti-melanoma showing cytotoxicity, anti-invasive effect inhibiting CAM angiogenesis, these novel findings contributing future research application this nanoplatform therapy.

Language: Английский

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Unveiling the Pharmacological Mechanism of Cosmos caudatus Compounds as Lung Cancer Drug Candidates: Pharmacology Networking, Molecular Docking, and Experimental Validation

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Cosmos caudatus is a traditional Indonesian medicinal plant commonly used in the treatment of cancer, hypertension, diabetes, osteoporosis, and other potential health conditions. However, mechanisms behind its compounds, targets, diseases, disease pathways, their molecular profiles treating lung cancer remain unclear. Therefore, comprehensive approach required to study these by integrating metabolomics, bioinformatics, vitro experimental validation explore active involved cancer. The metabolomic identified 66 compounds leaves, which 13 met criteria for gastrointestinal drugs. 3',4',5,7-tetrahydroxyflavone, AKT1 target, neoplasms PIP3 activating AKT signalling pathway, each became core target with highest degree value pharmacological network formed. In protein-protein interaction (PPI) network, again value. Gene Ontology (GO) functional enrichment analysis revealed that biological processes, functions, cellular components, KEGG pathways were phosphorylation, cytoplasm, protein binding, respectively. three best binding energy hydrogen bonding 3',4',5,7-tetrahydroxyflavone-AKT1 (9C1W), gamma-mangostin-EGFR (3P0V), cratoxyarborenone E-TNF (1XU1), energies -10.8, -8.9, − 9.6 kcal/mol, methanol extracts inhibited A549 cells at concentration 156.12 µg/mL. combination methods provides insights into C.

Language: Английский

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Unveiling the Pharmacological Mechanism of Cosmos Caudatus Compounds as Lung Cancer Drug Candidates: Pharmacology Networking, Molecular Docking, and Experimental Validation

Journal of Pharmaceutical Innovation, Journal Year: 2025, Volume and Issue: 20(3)

Published: April 21, 2025

Language: Английский

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Widely metabolomic combined with transcriptome analysis to build a bioactive compound regulatory network for the fruit growth cycle in Pseudocydonia sinensis

Food Chemistry, Journal Year: 2024, Volume and Issue: 456, P. 139933 - 139933

Published: May 31, 2024

Language: Английский

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Aspirin–Fisetin Combinatorial Treatment Exerts Cytotoxic and Anti-Migratory Activities in A375 Malignant Melanoma Cells

Medicina, Journal Year: 2024, Volume and Issue: 60(7), P. 1125 - 1125

Published: July 12, 2024

Background and Objectives: Malignant melanoma (MM) remains one of the most aggressive cancers worldwide, presenting a limited number therapeutic options at present. Aspirin (ASA), broadly used non-steroid anti-inflammatory medicine, has recently emerged as candidate for repurposing in cancer management, due to its potential treatment several neoplasms which include MM. Fisetin (FIS) is flavonoid phytoestrogen instilled with multispectral pharmacological activities, including potent anti-melanoma property. The present study aimed assess improved anti-neoplastic effect resulting from association ASA FIS MM therapy. Materials Methods: was conducted using A375 cell line an experimental model Cell viability assessed via MTT test. morphology confluence were evaluated bright-field microscopy. aspect nuclei tubulin fibers observed through immunofluorescence staining. irritant anti-angiogenic determined on chorioallantoic membrane chicken fertilized eggs. Results: main findings related herein demonstrated that 2.5 mM + (5, 10, 15, 20 µM) combination exerted higher cytotoxicity cells compared individual compounds, outlined by concentration-dependent massive reduction viability, loss confluence, shrinkage rounding, apoptotic-like nuclear features, constriction disruption filaments, increased apoptotic index, suppressed migratory ability. µM lacked inhibited blood-vessel formation ovo. Conclusion: These results stand first contributions combinatorial treatment.

Language: Английский

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Paraptosis—A Distinct Pathway to Cell Death

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11478 - 11478

Published: Oct. 25, 2024

Cell death is a critical biological process necessary for development, tissue maintenance, and defense against diseases. To date, more than 20 forms of cell have been identified, each defined by unique molecular pathways. Understanding these different essential investigating the pathogenesis diseases such as cancer, neurodegenerative disorders, autoimmune conditions developing appropriate therapies. Paraptosis distinct form regulated characterized cytoplasmic vacuolation dilatation cellular organelles like mitochondria endoplasmic reticulum (ER). It several signaling pathways, instance, those associated with ER stress, calcium overload, oxidative specific cascades insulin-like growth factor I receptor (IGF-IR) its downstream pathways comprising mitogen-activated protein kinases (MAPKs) Jun N-terminal kinase (JNK). has observed in diverse contexts, including development stress responses neuronal, retinal, endothelial, muscle cells. The induction paraptosis increasingly important anticancer therapy, it targets non-apoptotic tumor cells, which can be utilized to induce death. This approach enhances treatment efficacy addresses drug resistance, particularly cases where cancer cells are resistant apoptosis. Combining paraptosis-inducing agents traditional therapies holds promise enhancing overcoming suggesting valuable strategy therapy.

Language: Английский

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Quercetin Enhances 5-Fluorouracil-Driven Cytotoxicity Dose-Dependently in A375 Human Melanoma Cells

Life, Journal Year: 2024, Volume and Issue: 14(12), P. 1685 - 1685

Published: Dec. 19, 2024

Cutaneous melanoma (CM) represents a severe skin cancer with rising incidence at present and limited treatment options. 5-Fluorouracil (5-FU) is widely used, including for CM; however, the innate resistance of this to conventional therapy remains problematic. Quercetin (QUE) flavonoid that can sensitize cells antitumor agents such as 5-FU. However, potential sensitization capability CM 5-FU has scarcely been determined, investigated herein. Therefore, A375 were tested in terms their cell viability, confluence, morphological changes. Their nuclear cytoskeletal aspects, clonogenic potential, ovo properties also followed. The results showed 50% inhibitory concentrations (IC50s) QUE determined by proliferation assay 11.56 11.08 µM, respectively. addition (10 µM) (5–50 increased cytotoxic potential. A significant decline viability (up 43.51%), loss chromatin condensation dysmorphology, tubulin F-actin constriction, suppressed ability noted. + association was non-irritating chorioallantoic membrane an antiangiogenic effect ovo. Thus, our highlight combining enhance safe profile

Language: Английский

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